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Statistical tests for biomarker identification and classification methods for patient grouping are two important topics in adaptive designs of clinical trials related to genomic studies. In this article, we evaluate four test methods for biomarker identification in the first stage of an adaptive design: a model-based identification method, the popular two-sided t-test, the nonparametric Wilcoxon Rank-Sum test (two-sided), and the Regularized Generalized Linear Models. For patients grouping in the second stage, we examine classification methods such as Random Forest, Elastic-net Regularized Generalized Linear Models, Support Vector Machine (SVM), Gradient Boosting Machine (GBM), and Extreme Gradient Boosting (XGBoost). Simulation studies are carried out to assess the performance of the different methods. The best identification methods are chosen based on the well-known F 1 score, while the best classification techniques are selected based on the area under a receiver operating characteristic curve (AUC). The chosen methods are then applied to the Adaptive Signature Design (ASD) with a real data set from breast cancer patients for the purpose of evaluating the performance of ASD in different situations. [ABSTRACT FROM AUTHOR]

The central Great Xing'an Range contains widespread exposures of Mesozoic igneous rocks, yet the origin of its Late Mesozoic volcanic rocks has long been controversial. They are composed of andesite, trachyte, trachyandesite, trachydacite, rhyolite, and minor basaltic andesite. The intermediate rocks are enriched in large ion lithophiles and light rare earth elements (LILEs and LREEs) and are depleted in high field strength elements (HFSEs) such as Nb, Ta, and Ti, with positive εHf(t) values (+6.2 to +13.4) and Hf single-stage model ages (TDM1 = 556–227 Ma). This indicates that they were derived from the partial melting of a mantle wedge that was modified by previously subducted slab-derived fluids was likely introduced with limited crustal contamination. The felsic rocks show positive εHf(t) values (+4.3 to +10.2) and Hf two-stage model ages (TDM2 = 910–544 Ma), with more enrichment of LILEs and LREEs and more depletion of HFSEs and negative Eu anomalies. This indicates that felsic rocks were mainly derived from partial melting of Neoproterozoic accreted quartz-amphibolite facies mafic crust. We summarise the geochronological and Hf-Nd isotope data for Mesozoic igneous rocks within the central Great Xing'an Range (CGXR), the northern Xing'an block (NXB), and the Erguna block (EB), with the aim of constraining the geochronological framework for Mesozoic volcanism and comparing the growth of continental crust. The evolution of Late Mesozoic magmatism in the three areas reached its climax ~125 Ma ago. Our data, together with regional isotope evidence, suggest that crustal accretion of the CGXR occurred during the Neoproterozoic–Phanerozoic. However, that of the EB occurred during the Meso- to Neoproterozoic. The EB exhibits more lateral and vertical heterogeneities and ancient continental crust than the CGXR and NXB in the northern magma source region. [ABSTRACT FROM AUTHOR]

The Tayuan plutons located at the boundary of the Erguna and Xing'an blocks expose a coexisting mafic-felsic association that is made of monzogranite and gabbro-monzodiorite as well as subordinate quartz monzonite. LA-ICP-MS U-Pb zircon dating revealed a synchronous emplacement of the monzogranite (314-317 Ma), gabbro (308-315 Ma), and quartz monzonite (310 ± 3 Ma). The majority of these intrusions are characterized by an enrichment in light rare earth elements relative to heavy rare earth elements and a depletion of high strength field elements (e.g. Nb, Ta, Ti). Zircons from the gabbro and monzogranite have εHf(t) values of 1.1-9.6 and −3.0-3.3, respectively. Geochemical data show that the gabbro-monzodiorite may have been generated by the melting of a fluid-metasomatized lithospheric mantle, while the monzogranite may have been formed by a partial melting of the Mesoproterozoic crust. The quartz monzonite has similar whole-rock geochemical and Hf isotopic compositions to those of the gabbros and could have been produced from the same mantle source as that from which the gabbros were extracted. The Tayuan plutonic rocks have high contents of K2O and total alkalis and show a northwestward polarity like that of the continental margin plutonic rocks along the Hegenshan-Heihe suture zone. Combined with data from published studies, our data indicate that the Tayuan intrusive rocks were generated by the northwestward subduction of the Hegenshan-Heihe Oceanic plate. [ABSTRACT FROM AUTHOR]

This paper presents major element, trace element, and new zircon Hf isotopic data for the Early Mesozoic intrusive rocks in the south Hunchun, Yanbian area, Northeast China. These data are used to constrain the petrogenesis of these intrusive rocks and their implications for the Phanerozoic continental growth of the Central Asian Orogenic Belt (CAOB). Combining geology, geochronology, and whole-rock geochemistry, we identify three distinct episodes of magmatism as Early-Middle Triassic (249-237 Ma), Late Triassic (224-206 Ma), and Early Jurassic (200-187 Ma). The Early-Middle Triassic (249-237 Ma) adakitic tonalite and granodiorite were produced by the partial melting of subducted oceanic slabs, and the melts were contaminated by mantle peridotite during their ascent, whereas the coeval non-adakitic diorite and monzogranite were most likely derived from partial melting of crustal material. The remarkably high zircon Hf isotopic signature (εHf(t) = + 9.4 - +18.9), the enrichment in large-ion lithophile element and light rare earth elements, and the depletion in high field strength element suggest that these 224 Ma gabbros were derived from the partial melting of depleted mantle modified by subduction-related fluids. The 212 Ma monzogranite was most likely derived from juvenile material mixed with old crustal material as evidenced by their high SiO2, low MgO, and low Cr concentrations and variable εHf(t) values (-4.6 to +10.0). Except for the 197 Ma tonalites with affinity to the high silica adakites, the overall geochemical evolution of Early Jurassic (200-187 Ma) rocks was consistent with fractional crystallization from quartz diorite, granodiorite, and monzogranite to syenogranite. Both the Early Jurassic syn-subduction lateral continental growth by accretion of arc complexes and the Late Triassic post-collisional vertical continental growth by accretion of mantle-derived material played an important role in the Phanerozoic continental growth of the CAOB. [ABSTRACT FROM AUTHOR]

Studies investigating the association of milk consumption with bladder cancer risk have reported inconsistent findings. We conducted a meta-analysis of published cohort and case-control studies to pool the risk estimates of the association between milk intake and bladder cancer. We quantified associations with bladder cancer using meta-analysis of odds ratio (OR) associated with the highest vs. the lowest category of milk intake using fixed- or random-effect models depending on the heterogeneity of effects among studies. Nineteen cohort and case-control studies were eligible for inclusion. High milk intake was significantly associated with decreased risk of bladder cancer (OR, 0.84; 95% CI, 0.71–0.97) when comparing the highest with the lowest category of milk intake. The inverse association was stronger in Asia (OR, 0.60; 95% CI, 0.40–0.81) than North America (OR, 0.89; 95% CI, 0.76–1.03), and no association was observed in Europe (OR, 1.05; 95% CI, 0.85–1.26). This relationship also varied significantly by specific dairy products. Our results suggest that milk may be related to the reduction of bladder cancer risk. Further studies need to clarify the biological mechanisms. [ABSTRACT FROM PUBLISHER]